[show abstract][hide abstract] ABSTRACT: The influence of stereochemistry on the radical scavenging activity of catechins was investigated by studying the effect of pH on the antioxidant properties of catechin epimers. The difference in the pH-dependent Trolox equivalent antioxidant capacity (TEAC) profiles was observed only in case of gallocatechin gallate (GCG) and epigallocatechin gallate (EGCG), indicating the influence of steric structure on the TEAC antioxidant activity of these galloyl moiety-containing catechins. Based on comparison of the pH-dependent TEAC values to theoretically calculated parameters, including homolytic OH bond dissociation energy and ionization potential (IP) as well as theoretically predicted structures of the most stable monoanions of GCG and EGCG, it was concluded that due to steric hindrance in GCG molecule, the IP value of GCG monoanion increases reflecting lower radical scavenging capacity of GCG in comparison with EGCG. It results in the difference in the pH-dependent TEAC profiles of these two catechin epimers at pH above 3.5. This effect does not occur for other pairs of catechin epimers of this study.
European Food Research and Technology 08/2013; 235(6). · 1.44 Impact Factor
[show abstract][hide abstract] ABSTRACT: Chromium(III) is considered as an essential element playing a role in carbohydrate and lipid metabolism, and various chemical forms of this element are widely used in dietary supplements. A new trinuclear chromium(III) glycinate complex [Cr(3)O(NH(2)CH(2)CO(2))(6)(H(2)O)(3)](+)NO(3)(-) (CrGly), an analogue of Cr3 (trinuclear Cr(III) propionate complex) has been synthesized as a potential source of supplementary Cr. In this study, we evaluated the acute toxicity class of CrGly in Wistar rats applying the OECD 423 procedure. Male and female Wistar rats (n = 12, 6 ♀ and 6 ♂) were given by gavage either a single dose of CrGly 2,000 mg/kg body mass (equals to 300 mg Cr(III)/kg body mass; in aqueous solution) or equivalent volumes of distilled water and fed ad libitum commercial Labofeed B diet, and observed carefully for 14 days, then sacrificed to collect blood and internal organs for biochemical and histologic examination. No death cases were detected. No abnormalities in animal behavior, body mass gains, gross organ histology, or blood morphology and biochemistry were observed. The results demonstrate that LD(50) of CrGly is greater than 2,000 mg/kg when administrated orally to rat; thus, this compound appears to belong to the fifth category in the GHS system or the fourth class ("unclassified") in the EU classification system.
Biological trace element research 01/2011; 143(3):1564-75. · 1.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: In the present study, the ability of green tea catechins to induce electrophile-responsive element (EpRE)-mediated gene expression and the role of their quinones in the mechanism of this induction were investigated. To this end, Hepa1c1c7 mouse hepatoma cells were used, stably transfected with a luciferase reporter gene under the expression regulation of an EpRE from the human NAD(P)H:quinone oxidoreductase 1 (NQO1) gene. The results obtained show that several, but not all, catechins tested are able to induce EpRE-mediated gene transcription, with epigallocatechin gallate (EGCG) and gallocatechin gallate (GCG), both containing a pyrogallol and a galloyl moiety, being the most powerful inducers. Moreover, it was demonstrated that the EpRE-mediated response to catechins was increased in cells with reduced cellular glutathione (GSH) levels and decreased in cells with increased levels of GSH, corroborating a role for catechin quinones. The intrinsic capacity of catechins to form quinone type metabolites upon their oxidation was demonstrated using incubations of epigallocatechin (EGC) and EGCG with tyrosinase and the GSH-trapping method. Glutathione conjugates formed in these incubations were identified as 2'-glutathionyl-EGC, 2',6'-diglutathionyl-EGC, 2'-glutathionyl-EGCG, and 2',6'-diglutathionyl-EGCG, supporting the formation of quinone type metabolites involving especially the pyrogallol moiety of these catechins. Formation of the EGCG-quinone-glutathionyl adducts was also observed in the EpRE-LUX cellular system. This further supports the importance of the pyrogallol moiety for the quinone chemistry of the catechins. Finally, the presence of the pyrogallol moiety in the catechins also results in a relatively lower half-wave oxidation potential (E1/2) and calculated heat of formation (DHF) for conversion of the catechins to their corresponding quinones, pointing at an increased ability to become oxidized. Altogether, our studies reveal that catechins, especially those containing a pyrogallol moiety, induce EpRE-mediated detoxifying gene expression and that this induction is likely to be the result of their quinone chemistry.
Chemical Research in Toxicology 01/2009; 21(12):2352-60. · 3.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: The effect of pH on the radical scavenging capacity of green tea catechins was investigated using experimental as well as theoretical methods. It was shown that the radical scavenging capacity of the catechins, quantified by the TEAC value, increases with increasing pH of the medium. Comparison of the pKa values to theoretically calculated parameters for the neutral and deprotonated forms indicates that the pH-dependent increase in radical scavenging activity of the catechins is due to an increase of electron-donating ability upon deprotonation. The data also reveal that the radical scavenging activity of the catechins containing the pyrogallol (or catechol) and the galloyl moiety over the whole pH range is due to an additive effect of these two independent radical scavenging structural elements. Altogether, the results obtained provide better insight into the factors determining the radical scavenging activity of the catechins and reveal that the biological activity of green tea catechins will be influenced by the pH of the surrounding medium or tissues.
Journal of Agricultural and Food Chemistry 03/2008; 56(3):816-23. · 2.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: In the present study, the pH-dependent free radical-scavenging activity of betanin in the Trolox equivalent antioxidant capacity (TEAC) assay was determined. It was found that at a pH > 4 betanin is about 1.5-2.0-fold more active than some anthocyanins considered very good free radical scavengers as determined in the TEAC assay. The increase in the TEAC values of betanin with increasing pH is discussed in terms of its calculated phenolic OH homolytic bond dissociation energy (BDE) and ionization potential (IP). The results suggest that the exceptionally high antioxidant activity of betanin is associated with an increasing of its H-donation and electron-donation ability when going from cationic state to mono-, di- and tri-deprotonated states present at basic solutions.
Food Additives and Contaminants 11/2006; 23(11):1079-87. · 2.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: The radical scavenging capacity of red wine anthocyanins was quantified by the so-called TEAC assay with special emphasis on the influence of pH and conjugation on this activity. The pH appears to be a dominant factor in the radical scavenging capacity of wine anthocyanins, with higher pH values increasing this capacity significantly. On the basis of the pKa values for deprotonation and theoretical calculations, it could be concluded that the effect is due to an increase in intrinsic radical scavenging capacity upon deprotonation. The data also reveal that the reduction in radical scavenging activity of anthocyanins upon their conjugation can, at least in part, be ascribed to an increase in pKa values upon conjugation. Altogether, the results obtained provide molecular insight into factors that influence radical scavenging potential of anthocyanins and reveal that the radical scavenging-mediated supposed beneficial health effects of these wine pigments will be influenced by the pH of the surrounding matrix or tissue.
Journal of Agricultural and Food Chemistry 08/2005; 53(14):5526-34. · 2.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: In this study the effect of 3-O-β-glucosylation on the experimentally determined pKa and pKh values of cyanidin, malvidin, delphinidin were investigated using pH dependent UV–Vis spectroscopy. Structural transformations of cyanidin-type pigments from flavylium cation through the colorless chemiacetal and chalcone forms to the mixture of quinoidal-bases, were characterized on the basis of thermochemical parameters calculated by functional theory B3LYP method. The most stable molecular structures of cyanidin 3-O-β-glucoside and the role of intramolecular hydrogen bondings in stabilization of its different forms are discussed. The results explain how the stabilization of cyanidin 3-O-β-glucoside flavylium cation by the net of intramolecular H-bondings within sugar moiety and between sugar and anthocyanin molecule affects its structural transformations.
[show abstract][hide abstract] ABSTRACT: Ten crystalline complexes of N-methylmorpholine betaine with some benzoic acids (pKa from 0.65 to 4.85) have been synthesized and analyzed by 1H and 13C NMR spectroscopy in DMSO-d6 solution. 1H and 13C screening constants for complexes and benzoic acids and energies of complex formation have been calculated at the B3LYP/6-31G(d,p) level of theory. The linear correlations between the experimental proton and carbon chemical shifts and computed screening constants have been obtained, which allows an assignment of all resonance signals to the corresponding atoms.
Journal of Molecular Structure 01/2005; · 1.40 Impact Factor
[show abstract][hide abstract] ABSTRACT: The biological effect of flavonoids can be modulated in vivo due to metabolism. The O-methylation of the catechol group in the molecule by catechol O-methyl transferase is one of the important metabolic pathways of flavonoids. In the present study, the consequences of catechol O-methylation for the pH-dependent radical scavenging properties of quercetin and luteolin were characterized both experimentally and theoretically. Comparison of the pKa values to the pH-dependent TEAC profiles reveals that O-methylation not only affects the TEAC as such but also modulates the effect of changing pH on this radical scavenging activity due to an effect on the pKa for deprotonation. The pH-dependent TEAC curves and computer calculated electronic parameters: bond dissociation energy (BDE) and ionisation potential (IP) even indicate that O-methylation of the luteolin catechol group affects the radical scavenging potential only because it shifts the pKa for deprotonation. O-Methylation of the quercetin catechol moiety affects radical scavenging capacity by both an effect on the pKa, and also by an effect on the electron and hydrogen atom donating properties of the neutral (N) and the anionic (A) form of the molecule. Moreover, O-methylation of a catechol OH-group in quercetin and luteolin has a similar effect on their TEAC profiles and on calculated parameters as replacement of the OH-group by a hydrogen atom. Altogether, the results presented provide new mechanistic insight in the effect of catechol O-methylation on the radical scavenging characteristics of quercetin and luteolin.
Free Radical Research 07/2004; 38(6):639-47. · 3.28 Impact Factor
[show abstract][hide abstract] ABSTRACT: The effect of the pH on antioxidant properties of a series of hydroxyflavones was investigated. The pKa of the individual hydroxyl moieties in the hydroxyflavones was compared to computer-calculated deprotonation energies. This resulted in a quantitative structure activity relationship (QSAR), which enables the estimation of pKa values of individual hydroxyl moieties, also in hydroxyflavones for which these pKa values are not available. Comparison of the pKa values to the pH-dependent antioxidant profiles, determined by the TEAC assay, reveals that for various hydroxyflavones the pH-dependent behavior is related to hydroxyl moiety deprotonation, resulting in an increase of the antioxidant potential upon formation of the deprotonated forms. Comparison of these experimental results to computer calculated O-H bond dissociation energies (BDE) and ionization potentials (IP) of the nondeprotonated and the deprotonated forms of the various hydroxyflavones indicates that especially the parameter reflecting the ease of electron donation, i.e., the IP, and not the BDE, is greatly influenced by the deprotonation. Based on these results it is concluded that upon deprotonation the TEAC value increases (radical scavenging capacity increases) because electron-, not H*-, donation becomes easier. Taking into account that the mechanism of radical scavenging antioxidant activity of the neutral form of the hydroxyflavones is generally considered to be hydrogen atom donation, this implies than not only the ease of radical scavenging, but also the mechanism of antioxidant action changes upon hydroxyflavone deprotonation.
Free Radical Biology and Medicine 11/2001; 31(7):869-81. · 5.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: n this work we report the results of our study on electronic and spectral properties of conjugated polyenes with electron-accepting 1,3-dialkyl-2-thiobarbituric acid moiety. In model calculations, we examine the effect of the conjugated polyene length on infrared (IR) and Raman spectra of the polyenes by means of ab initio HF/3-21G*. Nonlinear properties were also studied by AM1 method in frames of the sum-over-states (SOS) and finite-field formalism. It was concluded that in well-resolved IR and Raman spectra the frequencies and band intensities can provide valuable information relating to CC bond lengths in polyene chain and relative polarizabilities. Near-linear correlation between polarizability and integral IR band intensity, corresponding to all CC stretching modes, and the rather nonlinear relationship of polarizability with integral Raman activity, was found. In our calculation we predict that polarizability and the first hyperpolarizability increases with elongation of polyene chain while the second hyperpolarizability increases smoothly in a quadratic way. In contrast to the linear relationship between polarizability and polyene chain length the dipole moment versus chain length is predicted to be nonlinear. A good agreement was found between experimental and calculated Raman spectra of one newly synthesized compound studied.
[show abstract][hide abstract] ABSTRACT: The chemical reactivity, isomerization, and glutathione conjugation of quercetin o-quinone were investigated. Tyrosinase was used to generate the unstable quercetin o-quinone derivative which could be observed upon its subsequent scavenging by glutathione. Identification of the products revealed formation of 6-glutathionyl-quercetin and 8-glutathionyl-quercetin adducts. Thus, in particular, glutathione adducts in the A ring of quercetin were formed, a result which was not expected a priori. Quantum mechanical calculations support the possibility that the formation of these glutathione adducts can be explained by an isomerization of quercetin o-quinone to p-quinone methides. Surprisingly, additional experiments of this study reveal the adduct formation to be reversible, leading to interconversion between the two quercetin glutathione adducts and possibilities for release and further electrophilic reactions of the quercetin quinone methide at cellular sites different from those of its generation.
Chemical Research in Toxicology 04/2000; 13(3):185-91. · 3.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: The influence of pH, intrinsic electron donating capacity, and intrinsic hydrogen atom donating capacity on the antioxidant potential of series of hydroxy and fluorine substituted 4-hydroxybenzoates was investigated experimentally and also on the basis of computer calculations. The pH-dependent behavior of the compounds in the TEAC assay revealed different antioxidant behavior of the nondissociated monoanionic form and the deprotonated dianionic form of the 4-hydroxybenzoates. Upon deprotonation the radical scavenging ability of the 4-hydroxybenzoates increases significantly. For mechanistic comparison a series of fluorobenzoates was synthesized and included in the studies. The fluorine substituents were shown to affect the proton and electron donating abilities of 4-hydroxybenzoate in the same way as hydroxyl substituents. In contrast, the fluorine substituents influenced the TEAC value and the hydrogen atom donating capacity of 4-hydroxybenzoate in a way different from the hydroxyl moieties. Comparison of these experimental data to computer-calculated characteristics indicates that the antioxidant behavior of the monoanionic forms of the 4-hydroxybenzoates is not determined by the tendency of the molecule to donate an electron, but by its ability to donate a hydrogen atom. Altogether, the results explain qualitatively and quantitatively how the number and position of OH moieties affect the antioxidant behavior of 4-hydroxybenzoates.
Free Radical Biology and Medicine 01/2000; 27(11-12):1427-36. · 5.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Polyphenolic antioxidants exhibited a dose-dependent toxicity against human promyelocytic leukemia cells (HL-60). Their action was accompanied by malondialdehyde formation, and was partly prevented by desferrioxamine and the antioxidant N,N'-diphenyl-p-phenylene diamine. This points to a prooxidant character of their cytotoxicity. A quantitative structure-activity relationship (QSAR) has been obtained to describe the cytotoxicity of 13 polyphenolic antioxidants belonging to three different groups (flavonoids, derivatives of gallic and caffeic acid): log cL50 (microM) = (2.7829+/-0.2339)+(1.2734+/-0.4715) Ep/2 (V)-(0.3438+/-0.0582) log P (r2 = 0.8129), where cL50 represents the concentration for 50% cell survival, Ep/2 represents the voltammetric midpoint potential, and P represents the octanol/water partition coefficient. Analogous QSARs were obtained using enthalpies of single-electron oxidation of these compounds, obtained by quantum-mechanical calculations. These findings clearly point to two important characteristics determining polyphenol cytotoxicity, namely their ease of oxidation and their lipophilicity.
[show abstract][hide abstract] ABSTRACT: Several model polyenes with modified indanone groups were studied by means of density functional theory (DFT) B3LYP/6-31G*, ab initio HF/3-21G* and semiempirical AM1 methods. We investigated the effect of several substituents upon the relationship between the structure, spatial distribution of the highest occupied and the lowest unoccupied π-MOs, a concept of the global softness and the global hardness as well as both linear and nonlinear polarizabilities for the set of π-electron chromophores represented by the short-chain model polyene (butadiene) carrying out p-methoxyphenyl group on the one end and several modified indanone groups on the opposite end of the molecule. As probing endocyclic groups used to modify the structure of indanone the following substituents: >CH2; >CO; >SO2, >CCH(NO2) and >CC(CN)2 were selected. The cubic relationship between the polarizability and the global softness was found. The highest polarizabilities (α, β, γ) are predicted for the derivatives with >CC(CN)2 group. It was found that the value of β depends mainly on the difference between dipole moments in the excited and ground states of the molecules. In the case of >SO2 group the results of AM1 calculations significantly deviate from relationships found for other derivatives. Experimental IR and Raman spectra of newly synthesized indandione derivative of cinnamaldehyde were compared with computed ones.